School of Medicine and Health Sciences Poster Presentations

Title

Sex Differences in the Peripheral Immune Response to Social Isolation Stress

Document Type

Poster

Abstract Category

Basic Biomedical Sciences

Keywords

immune system, lymphocytes, neuroimmune, psychology, social isolation stress

Publication Date

Spring 5-1-2019

Abstract

Introduction: Social isolation (SI) increases susceptibility to neuropsychiatric illnesses such as depression and anxiety. Various homeostatic imbalances, changes in neurological development, and changes in neurotransmitter release from social isolation stress likely contribute to the behavioral changes seen in such disorders. However, current therapies for these different psychological disorders are inadequate, highlighting the lack of complete understanding of the intricate pathways involved in the pathophysiology of such neuropsychiatric disorders. There is increasing evidence for the influence of immunological networks and inflammation on psychiatric disorders, but the exact mechanisms are not yet well understood. In the current study, using a rodent model of SI stress we characterized the peripheral immune response to social isolation stress. We hypothesized that SI stress would alter the peripheral immune cellular profile which would be influenced by biological sex. Methods: Male and female mice underwent two weeks of SI stress in which they were singly housed in standard cages. Control mice were housed in standard cages in groups of five mice per cage. Following SI, they were then tested in a battery of behavioral tests that assay social interaction, anxiety, and stress coping behavior. Brain, spleen, and blood samples were collected from all mice. Splenocytes were isolated and stained with adaptive immune cell markers (CD3-APC, CD4-FITC, CD62L-PE, CD45-PerCP-Cy5.5, CD44-PE-Cy7, CD8a-APC-Cy7, CD19-APC-Cy7) and innate markers (CD11b-Pacific Blue, CD11c-APC, F4/80-PE-Cy7) for fluorescence activated cell sorting (FACS). Effector memory cells were characterized as either CD3+/CD4+/CD44+/CD62L- or CD3+/CD8+/CD44+/CD62L-, and central memory cells were characterized as CD3+/CD4+/CD44+/CD62L+ or CD3+/CD8+/CD44+/CD62L+. FlowJo v10 software was used for analysis of data obtained from FACS. Results: FACS analysis showed no SI stress or sex differences in populations of CD3+,CD3+/CD4+, CD3+/CD8+, CD11c+, or B-lymphocytes. However, when we examined effector memory cells, the male SI group had increased percentage of CD4+ effector memory cells (44.38%) compared to male controls (32.36%) while the female SI group had a decreased percentage of effector memory cells (39.91%) compared to female controls (46.20%). We observed similar differences in CD8+ effector memory cells (male SI stress (27.65%) vs male control (15.61%) and female SI stress (15.75%) vs female control (25.48%)). Conclusion: These data suggest a shift towards an inflammatory immune profile (increased effector memory cells) following SI stress that is sex dependent. The impact an immunological memory (effector vs central) shift has on the neurobiological response to SI is not clearly understood. Further studies are needed to examine this neuroimmune cross-talk.

Open Access

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Presented at Research Days 2019.

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Sex Differences in the Peripheral Immune Response to Social Isolation Stress

Introduction: Social isolation (SI) increases susceptibility to neuropsychiatric illnesses such as depression and anxiety. Various homeostatic imbalances, changes in neurological development, and changes in neurotransmitter release from social isolation stress likely contribute to the behavioral changes seen in such disorders. However, current therapies for these different psychological disorders are inadequate, highlighting the lack of complete understanding of the intricate pathways involved in the pathophysiology of such neuropsychiatric disorders. There is increasing evidence for the influence of immunological networks and inflammation on psychiatric disorders, but the exact mechanisms are not yet well understood. In the current study, using a rodent model of SI stress we characterized the peripheral immune response to social isolation stress. We hypothesized that SI stress would alter the peripheral immune cellular profile which would be influenced by biological sex. Methods: Male and female mice underwent two weeks of SI stress in which they were singly housed in standard cages. Control mice were housed in standard cages in groups of five mice per cage. Following SI, they were then tested in a battery of behavioral tests that assay social interaction, anxiety, and stress coping behavior. Brain, spleen, and blood samples were collected from all mice. Splenocytes were isolated and stained with adaptive immune cell markers (CD3-APC, CD4-FITC, CD62L-PE, CD45-PerCP-Cy5.5, CD44-PE-Cy7, CD8a-APC-Cy7, CD19-APC-Cy7) and innate markers (CD11b-Pacific Blue, CD11c-APC, F4/80-PE-Cy7) for fluorescence activated cell sorting (FACS). Effector memory cells were characterized as either CD3+/CD4+/CD44+/CD62L- or CD3+/CD8+/CD44+/CD62L-, and central memory cells were characterized as CD3+/CD4+/CD44+/CD62L+ or CD3+/CD8+/CD44+/CD62L+. FlowJo v10 software was used for analysis of data obtained from FACS. Results: FACS analysis showed no SI stress or sex differences in populations of CD3+,CD3+/CD4+, CD3+/CD8+, CD11c+, or B-lymphocytes. However, when we examined effector memory cells, the male SI group had increased percentage of CD4+ effector memory cells (44.38%) compared to male controls (32.36%) while the female SI group had a decreased percentage of effector memory cells (39.91%) compared to female controls (46.20%). We observed similar differences in CD8+ effector memory cells (male SI stress (27.65%) vs male control (15.61%) and female SI stress (15.75%) vs female control (25.48%)). Conclusion: These data suggest a shift towards an inflammatory immune profile (increased effector memory cells) following SI stress that is sex dependent. The impact an immunological memory (effector vs central) shift has on the neurobiological response to SI is not clearly understood. Further studies are needed to examine this neuroimmune cross-talk.